The purpose of this research is to determine the effectiveness of two medications, tricyclic antitidepressants (TCA) and opioids, compared to a placebo in the treatment of postherpetic neuralgia. The specific aims are to compare the effects of opioids and TCA against placebo on pain, altered skin sensitivity, and affective and cognitive function. In addition, the study will determine if the presence of psychiatric co- morbidity, particularly depression, predicts the outcome of treatment with opioids, TCA, and placebo. We have studied the relationships between ongoing pain, alterations in thermal sensibility, and allodynia to mechanical and thermal stimuli of patients with, PHN to determine the role of peripheral and/or central mechanisms, in PHN. Ongoing pain ratings were obtained using a verbal score (0-10). Sensory tests were performed within the affected site, and the corresponding, contralateral, normal site. The area of mechanical allodynia was mapped with a cotton swab and pain, evoked by mechanical stimuli (soft hair brush, brass probe, von Frey hairs) was rated on a verbal scale of 1-10. Thermal thresholds to warm, cold, heat pain, and cold pain were determined using a Peltier device and a modified Marstock technique. To date, fifty-nine patients (33 F, 26 M) with PHN of 3-216 months duration (median = 19 months) have been studied. The average rating of ongoing pain was 7.3 + 2 (M + SD). The majority of patients (80%) had allodynia to dynamic (hair brush), static (brass probe) or punctate (von Frey) mechanical stimuli (Z > 5.01, p<.0001). No significant correlation was observed between the intensity of ongoing pain and mechanical allodynia. As a group, the patients demonstrated hypoesthesia to cold and warm detection, and hypoalgesia to heat pain and cold pain. There were no significant correlations between ongoing pain intensity and the degree of sensory alterations (between the unaffected and affected sites) in warm, cold, heat pain, and cold pain detection thresholds. Hence, the role of primary afferent input in tlie mechanism of PHN is uncertain. The presence of allodynia/hyperalgesia to mechanical stimuli, but the relative absence of hyperalgesia to thermal stimuli in most patients in this group suggests that central sensitization in PHN is not generalized for all modalities of sensation. It has been observed that patients with chronic pain have high rates of psychiatric conditions. Controversy has existed as to whether these conditions are uniquely related to chronic pain or simply the result of ongoing suffering from a chronic physical symptom. Patients completed a structured interview (DIS-III-A) for Major Depression, Dysthymic Disorder, Generalized Anxiety Disorder and Somatization Disorder and completed the Somatization and Anxiety subscales of the SCL-90-R. Our results in PHN patients are consistent with the existing literature. PHN patients compared to patients with chronic and distressing but non- pain physical symptoms also reported higher numbers of depression symptoms as well as other medically unexplained physical symptoms. These findings suggest that depression and higher levels of somatic focus are more than secondary complications of experiencing chronic symptoms and are uniquely related to chronic pain.